Biology subjects

Trevisiol, A.

Publications and source records attributed to Trevisiol, A..

5 recordsLinked to original sources

bioRxiv2025

Stable neuronal representations to repeated stimulation underlie cognitive resilience in Alzheimer's disease pathology

While Alzheimers Disease (AD) typically triggers cognitive decline, some individuals with significant AD pathology maintain normal cognition into late life. Understanding the neuronal underpinnings of such cognitive resilience would propel the development of interventions for delaying dementia. To this end, we used cognitive testing to identify a subset of cognitively resilient 13-month-old TgF344-AD rats (established AD) and their non-transgenic littermates, followed by Neuropixels recording from 8500 neurons during repeated somatosensory stimulation. Cognitively resilient TgF344-AD rats recruited fewer neurons yet displayed more stable neuronal representations during repeated stimulations in cortical excitatory and hippocampal inhibitory ensembles, with reduced excitatory spike burstiness during network activation and a distinct pattern of functional synaptic connectivity. These associations existed independently of amyloid and tau levels. For the first time, our study revealed neuronal population-level hallmarks of maintained cognition that may serve as a novel neurophysiological biomarker of cognitive resilience and a target for stabilizing cognition.

neuroscience↗

bioRxiv2022

Axo-vascular coupling mediated by oligodendrocytes

The high energy requirements of the cortical gray matter are met by the precise cooperation of neurons, glia, and vascular cells in a process known as neurovascular coupling (NVC). In contrast, the existence and significance of NVC in white matter (WM) are still debated and basic regulatory mechanisms are unknown. We recently discovered that oligodendrocytes sense the spiking axons activity via NMDA receptors and regulate their cell surface expression of glucose transporter GLUT1 allowing an increase in glycolytic metabolism that enables lactate release to metabolically support the axons. Here, we show for the mouse optic nerve (ON), a model WM tract, that the vascular support is also dynamically controlled. Axonal spiking activity induces small vessel dilations which are sustained for more than 20 minutes upon the ending of electrical stimulation. Pharmacological inhibition shows that the electrically evoked dilation is mediated by the prostaglandin E2 receptor EP4 and can be modulated by the oxygen concentration, as has been shown in the grey matter. Importantly, we found in ONs from conditional mouse mutants that oligodendroglial NMDA receptors are required for this type of neurovascular response, demonstrating a critical role of oligodendrocytes in coupling axonal activity to pericyte function. Reminiscent of NVC in cortical slices, the "axo-vascular" response is slower and may represent a more rudimentary form of neurovascular coupling.

neuroscience↗

bioRxiv2022

Myelin lipids as nervous system energy reserves

Neuronal functions and impulse propagation depend on the continuous supply of glucose1,2. Surprisingly, the mammalian brain has no obvious energy stores, except for astroglial glycogen granules3. Oligodendrocytes make myelin for rapid axonal impulse conduction4 and also support axons metabolically with lactate5-7. Here, we show that myelin itself, a lipid-rich membrane compartment, becomes a local energy reserve when glucose is lacking. In the mouse optic nerve, a model white matter tract, oligodendrocytes survive glucose deprivation far better than astrocytes, by utilizing myelin lipids which requires oxygen and fatty acid beta-oxidation. Importantly, fatty acid oxidation also contributes to axonal ATP and basic conductivity. This metabolic support by fatty acids is an oligodendrocyte function, involving mitochondria and myelin-associated peroxisomes, as shown with mice lacking Mfp2. To study reduced glucose availability in vivo without physically starving mice, we deleted the Slc2a1 gene from mature oligodendrocytes. This caused a significant decline of the glucose transporter GLUT1 from the myelin compartment leading to myelin sheath thinning. We suggest a model in which myelin turnover under low glucose conditions can transiently buffer axonal energy metabolism. This model may explain the gradual loss of myelin in a range of neurodegenerative diseases8 with underlying hypometabolism9.

neuroscience↗

bioRxiv2019

A role of oligodendrocytes in information processing independent of conduction velocity

Myelinating oligodendrocytes enable fast impulse propagation along axons as revealed through studies of homogeneously myelinated white matter tracts. However, gray matter myelination patterns are different, with sparsely myelinated sections leaving large portions of the axons naked. The consequences of this patchy myelination for oligodendrocyte function are not understood but suggest other roles in information processing beyond the regulation of axonal conduction velocity. Here, we analyzed the contribution of myelin to auditory information processing using paradigms that are good predictors of speech understanding in humans. We compared mice with different degrees of dysmyelination using acute cortical multiunit recordings in combination with behavioral readouts. We identified complex alterations of neuronal responses that reflect fatigue and temporal acuity deficits. Partially discriminable but overall similar deficits were observed in mice with oligodendrocytes that can myelinate but cannot fully support axons metabolically. Thus, myelination contributes to sustained stimulus perception in temporally complex paradigms, revealing a role of oligodendrocytes in the CNS beyond the increase of axonal conduction velocity.

neuroscience↗

bioRxiv2019

HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons

Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can bidirectionally be modulated by HCN channel blockers, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mice cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC50 40 {micro}M; estimated endogenous cAMP concentration 13 {micro}M). In accord, immunogold-electron microscopy revealed HCN2 as the dominating subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2 channels control conduction velocity primarily via altering the resting membrane potential and was associated with significant metabolic costs. These results suggest that the cAMP-HCN pathway provides neuromodulators an opportunity to finely tune energy consumption and temporal delays across axons in the brain.

neuroscience↗